Metformina minimiza as alterações morfométricas no músculo sóleo de ratos submetidos à imobilização articular

Abstract

A proposta deste trabalho foi avaliar o músculo sóleo (S) de ratos submetidos à imobilização articular por sete dias, associado ou não ao tratamento com metformina (MET, 1,4mg.ml -1 ) por meio de análises morfométricas. Ratos adultos Wistar (n = 5) foram divididos nos grupos: controle (C), imobilizado em posição neutra do tornozelo (I), tratado com metformina (M), imobilizado tratado com metformina (I + MET). Foram avaliadas a área das fibras, a densidade de área do tecido conjuntivo intramuscular e a massa muscular do S. A análise estatística foi realizada pelo teste de normalidade, ANOVA e de Tukey (p < 0,05). A imobilização reduziu o peso muscular (mg) do S (34%). No grupo M não houve alteração significativa do peso muscular quando comparado com o grupo C. Já no grupo I + MET foi observado aumento do peso muscular em 29,6% quando comparado com o grupo I. O tratamento com metformina não alterou a área da fibra muscular quando comparado com grupo C. Já no grupo I, houve redução de 44% na área da fibra. Com relação ao grupo I + MET, houve aumento de 22% quando comparado com o grupo I. Por outro lado, ao compararmos o grupo C com o grupo I + MET, houve redução de 31%. Ao avaliar a densidade de área do tecido conjuntivo, observou-se que o grupo I apresentou elevação de 216% quando comparado com o grupo C. No grupo I + MET, houve redução de 67% comparado com o grupo I. O tratamento com metformina em músculos submetidos à imobilização minimizou a redução da área das fibras do S, bem como o aumento do tecido conjuntivo. Esses resultados sugerem que a metformina pode favorecer recuperação mais rápida na fase pós-imobilização.Palavras-chave: atrofia, desuso, metformina, reabilitação.. ABSTRACTThe aim of this study was to evaluate the effect of metformin treatment on the muscle mass, fibers area and connective tissue area density in soleus (S) muscle under articular immobilization. Methods and Results: Male Wistar rats (250-300g) were divided in 4 groups (n=5): control, treated with metformin, immobilized and immobilized treated with metformin. Immobilization was performed by acrylic resin orthoses on the left hindlimb keeping the ankle in neutral position during 7 days. The animals were euthanatized and the S muscle was dissected and weighed. Samples of its ventral portion were treated for inclusion in paraffin and stained in Hematoxylin-Eosin (H:E). The results were obtained through analyses of the muscular fiber area (images analyzed -Image Pró-plus 4,0), as well as of intramuscular connective tissue by means of planimetry. The statistical analysis was performed by normality test followed by ANOVA and Tukey (p<0.05). Hindlimb immobilization during 7 days promoted significant reduction (p<0.05) of 35% in the muscular mass; 44% (p<0.05) in the fiber area and increase of 216% (p<0.05) in the intramuscular connective tissue. The metformin in immobilized group promoted significant alterations (p<0.05) in the muscular mass. In addiction, it was observed significant increase (p<0.05) of 29.6% in the fibers area and signific...

Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle

“…This is consistent with other studies in young adult rodents such that MET was able to reduce fibrosis caused by high fat feeding 25 and limb immobilization. 7 Intramuscular fibroblasts are primarily responsible for collagen and ECM deposition in skeletal muscle. Due to the known coordination of fibroblasts and satellite cells, 21,22 it is possible that the MET + LEUmediated accumulation of satellite cells may have promoted downstream regulation of collagen content.…”

“…1,37 We found that MET + LEU treatment alleviated whole body strength and soleus force loss during disuse and was independent of changes to muscle or fiber size. We were surprised that muscle or fiber size was not altered by the dual treatment, since MET has previously been effective to ameliorate muscle atrophy caused by limb immobilization, 7 high fat feeding 25 and burn injury. 6 Similarly, LEU is a potent stimulator of muscle protein synthesis 11 and, in combination with antioxidant cocktail, was able to prevent disuse-induced muscle atrophy in adult rats.…”

“…In rodents, MET has demonstrated promise to improve skeletal muscle outcomes in response to atrophic stimuli yet appears to blunt muscle adaptations to exercise in humans 4 . However, MET has shown to prevent cardiotoxin‐induced muscle damage, 5 promoted muscle mass recovery from burn injury, 6 and prevented muscle mass loss and muscle fibrosis due to limb immobilization, 7 thus alluding to MET being uniquely beneficial during tissue damage or atrophy. Mechanistically, MET activates AMP‐activated protein kinase (AMPKα) and PPARG coactivator‐1alpha (PGC‐1α) in skeletal muscle tissues and cells 8,9 .…”

Resistance exercise recovery morphology and AQP1 expression in denervated soleus muscle of Wistar rats

“…The GIMP (GNU Image Manipulation Program) 2.0 (GNU General Public License ® , Berkeley, California) program was used to analyse the density of the connective tissue of the endomysium and perimysium (Bosi et al, 2008). The relative area of connective tissue (area density) was calculated by dividing the total number of pixels in the photomicrograph by the total of pixels marking connective tissue.…”

PGC-1α-Targeted Therapeutic Approaches to Enhance Muscle Recovery in Aging

“…Currently, research exploring metformin to prevent disuse atrophy and promote muscle recovery in aging at least in rodents appears to be strong. During 7 days hindlimb immobilization in young adult rats, metformin treatment ameliorated muscle atrophy and prevented tissue fibrosis [ 97 ]. In another study, rats treated with metformin during 16 weeks of high fat diet was effective to counter myofiber atrophy, fibrosis and increased E3 ubiquitin ligases expression compared to the non-metformin treated group [ 98 ].…”